Abstract: 
Atorvastatin calcium (ATR) is the choice of an anti-hyperlipidemic agent having only 12% oral bioavailability because of its poor aqueous solubility (log P 5.7) and extensive first-pass metabolism. The prime motivation for this work was to develop nanostructured lipid carriers (NLCs) to enhance solubility and avoid first-pass metabolism on oral administration of ATR. Amongst various lipids, stearic (solid) and oleic acid (liquid) were screened to prepare five different batches of ATR loaded lipidic nanoparticles (ATR-LPs) by employing hot homogenization technique for four homogenization cycles and at a pressure of 500 bar. Results concluded that as content of oleic acid increased from 0-30%, there was a decrease in particle size with increase in zeta potential, entrapment efficiency, and drug loading capacity. The optimized ATR-NLCs showed mean particle size of 147.8±7.4, PDI of 0.211±0.050 with a zeta potential of -22.5±3.64 mV. Compatibility was studied by Fourier transform infrared (FTIR) spectroscopy technique. Powder X-ray diffraction and differential scanning calorimetry studies which revealed that the crystalline ATR has converted into an amorphous form in ATR-NLCs. SEM photomicrographs confirmed the non-spherical shape of ATR-NLCs. In vitro dissolution study of ATR-NLCs established the biphasic release pattern. Triton-induced hyperlipidemic model was used for examining in vivo pharmacodynamic activity of ATR-NLCs, results of which was found to be significant than plain ATR suspension, making NLCs as a robust, promising perspective colloidal vehicles for oral delivery of ATR. Accelerated stability studies proved the robustness of ATRNLCs on three months storage at 25±2°C/60±5 % RH.

Keywords: Atorvastatin Calcium, Lipidic Nanoparticles, Nanostructured Lipid Carriers, High-Pressure homogenization, Pharmacodynamic Study, Triton-induced Hyperlipidemic Model, Accelerated Stability Studies.